IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection
bioinformatics molecular biology
Authors: Rosa et al.
Tags: Bioinformatics, Molecular biology
SARS-CoV-2-infected rhesus macaques have a distinct transcriptomic profile compared to healthy animals.
SARS-CoV-2-infected juvenile rhesus macaques have a different transcriptomic profile (upregulated genes associate with type I IFN signalling and Notch signalling) to old infected macaques (downregulated genes associated with VEGF signalling)
Transcriptomic comparison between COVID-19-positive patients and patients with tuberculosis showed that genes associated with neutrophil accumulation and IFN signalling are upregulated in both disease while genes associated with blood vessel morphogenesis and angiogenesis are upregulated only in COVID-19
Authors analysed the transcriptomic profile in 3 juvenile and 5 old SARS-CoV-2-infected rhesus macaques and compared it to naïve animals. Genes associated with neutrophil degranulation, type I IFN signalling and innate immune system were upregulated, while genes related to collagen degradation and TGFβ signalling were downregulated, in SARS-CoV-2-infected macaques compared to healthy controls. When comparing juvenile and old infected macaques, juvenile primates upregulated expression of type I IFN and Notch signalling-associated genes, while the old macaques downregulated genes associated with VEGF signalling. This may be surprising as elderly COVID-19 patients have increased plasma protein levels of VEGF.
Impact for SARS-CoV2/COVID19 research efforts
Understand the immune response to SARS-CoV2/COVID19
In vivo study (NHP)
Patient Case study
Strengths and limitations of the paper
Novelty: Mapping of the transcriptomic profile in juvenile and old rhesus macaques.
Standing in the field:In agreement. Neutrophil degranulation, type I IFN response and innate immune system were previously recognized to play a role in immunopathology associated with severe COVID-19. Downregulated VEGF signalling in old infected macaques may be conflicting their own finding that VEGF plasma levels are upregulated in elder COVID-19 patients. This difference may be due to species or tissue differences.
Appropriate statistics:Seems appropriate. Not fully explained what method they used formultiple testing correction.
Viral model used:SARS-CoV-2
Translatability:The transcriptomic data can contribute to the predictions about the immune response following SARS-CoV-2 infection needed for drug development/repurposing.
Main limitations: 1) This is an observational study; they report correlations between gene expression and the disease. The transcriptomic data require functional validation. For example, this study found a linear correlation between ACE2 and ADAM17 expression, however, did not discuss and test what this finding might functionally mean.
2) Deeper comparison to human transcriptomic data might be informative.